DNA sequencing of a cytogenetically normal acute myeloid leukemia genome

By T. Ley, Elaine R. Mardis, Li Ding, B. Fulton, M. McLellan, Ken Chen, D. Dooling, Brian H. Dunford-Shore, S. McGrath, M. Hickenbotham and 38 more. 2008

1,410 citations recorded by the source corpus.

Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient’s skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

Subfields: Cancer Research, Genetics, Hematology

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Michael R. Stratton

Citations in the corpus

ChIP-Seq: advantages and challenges of a maturing technology (2009, methodology): “Next-generation sequencing has already been applied in many areas, including the sequencing of whole genome”
VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. (2012, methodology): “Filter-passed somatic mutations were annotated using gene structure and UCSC (Karolchik et al. 2003) annotation information, assigning each mutation to one of four tiers as previously described (Ley et al. 2008; Mardis et al. 2009).”
Targeted Capture and Massively Parallel Sequencing of Twelve Human Exomes (2009, neutral): “These confirmation rates are , 10% higher than recent whole genome analyses 12,19–22 .”
Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution (2009, background): “01) Amplification (4) USP28 Ubiquitin carboxylterminal hydrolase 28 11:113185109 WGSS, WTSS C.”
Somatic mutation of EZH2 (Y641) in Follicular and Diffuse Large B-cell Lymphomas of Germinal Center Origin (2010, neutral): “Advances in DNA sequencing technology have recently enabled the characterization of genomes and transcriptomes at sufficient resolution for identification of somatic point mutation”
Biology, risk stratification, and therapy of pediatric acute leukemias: an update. (2011, background): “Genome-Wide Analysis The initial whole-genome sequencing of an adult with M1 AML and normal karyotype disclosed 10 somatic mutations and two leukemia-specific SNPs.(86) Two of the mutations involved FLT3 and NPM1, whereas the other eight genes involved nonsense and missense mutations that had not pr”